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68 Cards in this Set
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What is metabolism?
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the set of chemical reactions that occur in living organisms to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories. Catabolism breaks down organic matter, for example to harvest energy in cellular respiration. Anabolism, on the other hand, uses energy to construct components of cells such as proteins and nucleic acids
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What is synthesis?
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conversion of potential chemical energy into kinetic
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Name 3 physiological processes of whole organism metabolism?
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respiration, digestion, excretion
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Foods do what?
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renew energy expenditures, maintain body mass, provide growth and development, provide vitamins, minerals, salts and water
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What is free energy?
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energy liberated by complete oxidation of a food, expressed in caloreies / mole of substance
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What are three nutrients?
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Carbs, lipids, and proteins
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How much of the cell's dry weight does protein take up?
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50%
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What are some functions of protein?
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Structural proteins, enzymes, nucleoproteins, transport proteins, proteins that cause muscle contraction, plastic function:synthesis and renewal of structural parts of cell, energy production by oxidation
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What are some features of amino acids?
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Building blocks of protein, 20 different amino acids are found in body proteins, 10 amino acids can by synthesized in body: glycin, alanine, serine, cysteine, aspartic acid, glutamic acid, asparagine, glutamine, tyrosine, proline; 10 amino acide cannot be synthesized in sufficient quanitty: threonine, methionine, valine, leucine, isoleucine, lysine, arginine, phenilalanine, tryptophan, histidine
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Transport and storage of amino acids:
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normal concentration of amino acids in blood is between 35-65 mg/dl; transport of amino acids by diffusion through the pores, facilitated transport, active transport
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Homeostasis of blood amino acids maintained by?
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active renal reabsorption; usage of free amino acids for protein synthesis as a main form of storage in liver, kidney, and intestinal mucosa; resistance of structural proteins, collagen and muscles proteins to lysosomal digestive enzymes; excess of amino acids after protein limits are reached used for energy producation or converted to glycogen or lipids as a form of storage
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Endocrine regulation of plasma amino acids concentration:
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Growth hormone, testosterone, and insulin increasee protein synthesis; adrenaline, thyroxin, and glucocortitoids increase the concentration of plasma amino acids
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nitrogen balance:
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correlation between nitrogen entered into body and excreted from it; protein is main source of nitrogen in human body; protein contains 16%nitrogen, 6.25 g protein contains 1 g nitrogen; quantity of nitrogen multiplied by 6.25 is equal quantity of protein; total nitrogen is measured in urine; nitrogen equillibration- healthy adult; positive nitrogen balance- young poeple and children, pregenant women, healting aftger surgery and recuperation after severe disease, intensive sport training; Negative nitrogen balance- protein starvation
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What is obligatory degradation of protein?
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Rubner coeffecient: minimum body protein depletion in resting state is equal 0.028-0.075 g nitrogen per 1 kg body weight per 24 hoursd
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how much protein is recommended per day to maintain nitrogen equilibriation?
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30-60 grams
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What are the biochemical mechanisms of protein metabolism?
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Use of proteins for energy production; deamination; transamination; urea cycle; oxidation of deaminated amino acids; gluconeogenesis; ketogenesis
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What are the final products of protein metabolism?
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urea, uric acid, creatinine
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Urea cycle?
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free ammonia, the highly toxic product of protein catabolism is converted in to urea in hepatocytes and excreted by kidney into urine; ammonia that is not converted to urea may be incorporated into glutamine and undergo process of transamination; initial 3 steps of urea formation take place in mitochondria another 4 are functioning in cytoplasm in cyclic manner
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formation of carbamoyl phosphate?
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requires 2 enzymes: amino acid acetyltransferase and carbamoyl-phosphate syntase 1 (cpsi); aminto acid acetyltransferase forms N-acetyl glutamate an obligatory positive effector of CPSI
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ATP is required for activation of what?
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bicarbonate and forming of enzyme-bound carboxylphosphate that reacts with ammonium ion to form carbamate with elimination of inorganic phosphate; 2-d ATP reacts with enzyme-bound carbamate and carbamoyl phosphate is generated
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Formation of citrulline?
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Carbamoyl phosphate condensate with ornithine to yield citrulline
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Formation of Argininosuccinate, Arginine and Fumarate?
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In cytoplasm Citrulline condensate with Aspartate to form argininosuccinate
argininosuccinate lyase catalyzes cleavage of argininosuccinate to arginine and fumarate |
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Formation of Urea and Ornithine?
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Irreversible reaction catalyzed by arginase in cytozol forms urea and ornithine from arginine.
Ornithine reenter mitochondria and initiates next revolution of urea cycle |
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Hyperammonemias?
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Caused by inborn errors ureagenesis organic acidemias, liver immaturity and liver failure
Neonatal ammonemias are characterized by vomiting, lethargy, lack of appetite, seizures and coma |
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Inborn errors?
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Inborn errors of the six enzymes of ureagenesis and NAG synthase have been described . Inheritance pattern of the last is unknown, but 5 of urea cycle defects are autosomal recessive and ornithine carbamoyl transferase deficiency is X-linked (several thousands women in USA are carriers)
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Hyperammonemia?
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Acute neonatal hyperammonemia is a medical emergency and requires rapid lowering of ammonia level
Measures: hemodialysis,exchange transfusion, peritoneal dialysis, arginine hydrochloride administration Goals: decrease N intake, supplement arginine intake, promote N excretion in forms other then urea (hippurate) |
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Metabolism of Carbohydrates. Energy production?
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Main role of carbohydrates is their energy function
Glucose is main monosaccharide transported into tissue cells Level of blood glucose 4.4-6.7 mmole/L (80-120mg/100ml) is the most important homeostatic constant of human organism. Hypoglycemia: decrease in glucose level to 40-50 mg/100 ml can cause excessive sweat, lost of consciousness, seizure Hyperglycemia: nutritional hyperglycemia - increase in blood glucose level up to 160-180mg/100ml causes Glucose urea – glucose excretion with urine |
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Glucose transport:
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Facilitated diffusion is a major way of glucose transport through cell membranes: glucose molecule binds to the protein carrier and penetrate from one side of membrane to other and then released
Diffusion by concentration gradient: from side with high concentration to the site with low concentration Diffusion against concentration gradient: occurs only in gastrointestinal membranes and in renal tubules, so called active sodium –glucose co-transport (active transport of sodium provides energy for absorbing glucose against a concentration difference |
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Regulation of Carbohydrates by Metabolism
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Receptor of blood vessels, liver and hypothalamus are sensitive to changes in blood glucose level.
Insulin – the only hormone that decreases blood glucose level by increasing its transport to cells and synthesis glycogen in liver and muscles, increases utilization of glucose by cells. Diabetes – decrease in insulin secretion by beta-cells of pancreas Glucagon – increases blood glucose level. Secreted by alpha-cell of pancreas. Epinephrine, glucocorticoids, growth hormone, hormones of thyroid gland are antagonists of insulin. |
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Diabetes Type 1?
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Type 1diabetes – insulin –dependent diabetes mellitus is caused by lack of insulin autoimmune disorder: increase blood glucose causes dehydration of cell by increasing osmotic pressure; loss of glucose with urine increases thirst. Increased utilization of Fats leads to ketosis, diabetic coma and death. Proteins storage is decreased as well.
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Diabetes type 2?
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Type 2 –non-insulin-dependent is caused by decreased sensitivity of tissues to the metabolic effect of insulin. High insulin level in plasma (ketosis usually is not present). Obesity.
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Hyperinsulinism?
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Excessive insulin production from adenoma of islets.
Insulin shock :glucose level falls to50-70 mg/dl sweat, trembles, loss of consciousness can occur. Treatment :intravenous administration of large quantities of glucose, glucagon or epinephrine |
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Biochemical pathways of glucose metabolism in cell?
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Glycolysis – anaerobic way of glucose breakdown to 2 molecule of pyruvic acid and formation of 2 ATP molecules
Citric acid cycle (Krebs cycle) – aerobic way of glucose breakdown to final products CO2 and H2O and formation 36 molecules of ATP. Gluconeogenesis- glucose de novo synthesis from lactate pyruvate or amino acids Glycogenesis – process of glycogen formation |
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Glycolysis?
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Takes place in all tissues
Ten reactions occur in cytoplasm and are anaerobic culminate in 2 pyruvate molecule from each glucose molecule In cells that lack mitochondria (erythrocytes red blood cells) and in cells that contain mitochondria but under limiting conditions of oxygen- hypoxia (muscles during heavy exercise) end product is lactate |
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First phase of glycolysis?
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1 -phosphorylation of glucose (irreversible reaction accompanied by loss of free energy as a heat) by glucokinase (liver, pancreas) or hexokinase (muscles).
2 – isomerization of glucose-6-phosphate to fructose –6-phosphate by glucose phosphate isomerase. Reversible reaction. 3 – phosphorylation fructose-6-phosphate to fructose- 1,6-biphosphate catalyzed by 6-phosphofructokinase essentially irreversible reaction. 4 – cleavage of fructose-1,6-biphosphate into two triose phosphates catalyzed by aldolase, results in formation glyceraldehyde –3- phosphate and dihydroxyacetone phosphate 5 – triose-phosphate isomerase converts dihydroxyacetone phosphate into glyceraldehyde –3- phosphate reversible reaction that concludes the first phase of glycolysis One molecule of glucose yields 2 triose phosphates and 2 molecule of ATP are consumed |
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Second phase of glycolysis?
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6 –dehydrogenation of glyceraldehyde-3-phosphate to 1,3- bisglycerophosphate and formation NADH by glyceraldehyde phosphate dehydrogenase – reversible reaction
7 –phosphorylation of ADP from 1,3- bisglycerophosphate : phosphoryl group is transferred to ADP by phosphoglycerate kinase. The result is formation of two molecules ATP from one molecule of glucose and 3- phosphoglycerate –reversible reaction. 8 – isomerization of 3-phosphoglycerate to 2-phosphoglycerate by phosphoglycerate mutase 9- dehydration of 2-phosphoglycerate to phosphoenolpyruvate by enolase reversible reaction 10 – phosphorylation of ADP from phosphoenolpyruvate by pyruvate kinase: irreversible reaction that forms pyruvate and ATP Reduction of pyruvate to lactate reversible reaction is the final step of glycolysis and is catalyzed by LDH |
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Anaerobic glycolysis in various tissues and cells?
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Glycolysis is the predominant pathway providing ATP in cell and tissues that lack mitochondria: erythrocytes, lymphocytes, skeletal muscles , kidney medulla, skin and fetal neonatal tissues, some rapidly growing tumor cells
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Aerobic oxidation?
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Takes place in mitochondria
Convertion of pyruvic acid to Acetyl –CoA : pyruvate is transported into mitochondria and undergoes oxidative decarboxylation by enzymes of pyruvate dehydrogenate complex – physiologically irreversible reaction TCA cycle |
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Citric Acid cycle?
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Sequence of chemical reactions in which the acetyl portion of acetyl-CoA is degraded to carbon dioxide and hydrogen atoms. Occurs in mitochondria matrix
Released hydrogen atoms will be oxidized to form water and synthesize tremendous amount of ATP the high energy molecules |
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Stages of TCA begin with:
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Acetyl CoA combines Oxaloacetate to form Citric acid;
citrate is converted to isocitrate; isocitrate forms ketoglutarate; ketoglutarate is converted to succinate; succinate to fumarate; fumarate to malate which is converted to oxaloacetete During TCA cycle 4 CO2 (decarboxylases) , 16 H2, 2 acetylCoA molecules are released and 2 ATP are formed |
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Role of H2?
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Oxidation to H2O. they are combined with with nicotinamide dinucleotide (NAD+) which is part a specific enzyme –dehydrogenase and enter into multiple reaction that forms tremendous quantities of ATP
part of H2 atoms is combined with another dehydrogenase that has FAD+ (flavin adenin dinucleotide) as active center. |
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Chemiosmotic mechanism of the mitochondrial ATP formation?
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Oxidative phosphorylation, Electron transport chain:
-H2 is ionized to H+ one of 2 H is connected to NAD+ forms NADH another is free - 2 electrons released from H2 enter electron transport chain of electron acceptors in inner membrane of mitochondrion until it riches cytochrom oxidase –enzyme that reduces Oxygen to O2- which combines with H+ and forms H2O |
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Hydrogen pump?
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Energy released as electrons pass through chain is used to pump H+ from inner membrane of mitochondrion to outer chamber between two membranes which creates highly positively charge on the surface of inner membrane and negatively charged surface in inner matrix.
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ATP formation:
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ADP is converted to ATP by ATP synthetase
Electrical potential energy is used to bond ionic phosphate radical to ADP So formed ATP molecule is transported by facilitated diffusion into matrix of cell while ADP is transported into mitochondria |
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Efficiency of energy transfer from aerobic glucose breakdown:
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38 ATP molecules is formed from 1 molecule of glucose degraded to CO2 and H2O
66% of energy accumulated in ATP 34% of energy becomes a heat. |
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Oxygen deprivation:lactosis?
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If oxygen is unavailable or insufficient pyruvate and NADH is accumulated in cell. These two products are reacting and form lactate which diffuses to body fluids. This allow extra ATP formation during oxygen deprivation that can save life for several minutes in absence of respiratory oxygen.
When oxygen is available lactate is converted to pyruvate or used for gluconeogenesis- glucose formation |
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Pentose Phosphate pathway?
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Occurs in liver and fat cells alternative independent pathway for energy metabolism
The H2 released during pentose phosphate cycle combines with NADP+ (nicotinamide adenine dinucleotide phosphate) so formed NADPH can be used for synthesis of fats from carbohydrates and it is storage in the body. |
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Lipid Metabolism?
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Lipids include: neutral fat or triglycerides, phospholipids, cholesterol and other fatty acids.
Cholesterol do not contain fatty acid its sterol nucleus is synthesized from portions of fatty acid molecules and has similar properties of lipid substances Lipids mainly used for energy (produce twice more heat then carbs and proteins) and plastic (are parts of cellular membrane) purposes in cells Normal body fat is 10-20% of body weight |
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Transport of lipids?
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From intestine lipids are absorbed into intestinal lymph
Triglycerides are split into monoglycerides and fatty acids resynthesized into new triglycerides form droplets called chylomicrons. Chylomicrons enter blood stream Chylomicron are removed from blood by passing liver and adipose tissue Lipoprotein lipase synthesize hydrolysis triglycerides to fatty acids and glycerol, in such form they enter liver or adipose tissue cells and resynthesized back to triglycerides for storage |
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Regulation of fat transport from depot to tissues?
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Mainly in form of free fatty acids (by hydrolysis to glycerol and FFA)
The hydrolysis is stimulated by low glucose concentration and low formation of a-glycerophosphate –product of glucose breakdown. Hormone activated lipase activity: epinephrine and norepinephrine, growths hormone, thyroxin Inhibition of lipase activity by glucocorticoids and insulin Hypothalamus controls lipids metabolism: stimulation of appropriate centers leads to increase of lipolitic activity. Stimulation of sympathetic nervous system decreases fat accumulation; parasympathetic – increases |
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beta-oxidation?
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Oxidation of fatty acids(FA) takes place in mitochondria
Carnitine is a carrier substance for FA Degradation of FA release two-carbon segments in form of Acetyl-CoA Acetyl-CoA enters TCA |
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Ketosis?
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Two molecule of Acetyl-CoA condense to form one molecule of acetoacetic acid.
Acetoacetic acid can be converted to beta-hydroxybutyric acid. And acetone. All three substances diffuse to blood and being transported to peripheral tissues can be used for oxidation in TCA cycle. Enhanced level of Acetoacetic, beta-hydroxybutyric acids and acetone is a condition called ketosis (all are ketones by nature) (Acetone breath in diabetes patients) Ketosis occur when carbohydrates are not used for energy and in diabetes |
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Phospholipids?
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Composed with FA molecule, phosphoric acid radical and nitrogenous base: lecithins, chephalins and sphingomielin
Used for: -structural purpose: cell membranes especially in nervous tissue |
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Cholesterol?
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Exogenous cholesterol (food)
Endogenous cholesterol – synthesized by liver. Used for: membranes structure, cholic acid synthesis, adrenocortical hormones synthesis, male and female hormones synthesis |
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Artherosclerosis?
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Cholesterol plaques development on inner walls of blood vessels can lead to atherosclerosis. Calcium salts and other lipids deposits can precipitate in plaques sites and increase them in size to interfere with free blood circulation and promoting blood clots.
Cause: daily diet high in saturated fat or genetic disorder in formation low-density lipoprotein receptors on the cell’s membrane. |
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Prevention of artherosclerosis?
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Low-fat diet
Drug therapy Diet rich in fiber (oat bran |
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Liver role in metabolism?
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Carbohydrate metabolism
Fat metabolism Protein metabolism Blood coagulation factors synthesis Excretion Detoxication Digestion (formation of bile) Blood deposition Vitamins synthesis |
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Vitamins?
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Vitamins are organic compounds that take part in metabolism mainly because their role as a cofactors of important enzyme complexes.
Storage of vitamins is limited, especially water soluble vitamins |
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Mineral metabolism?
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Magnesium cofactor of enzymes in carbohydrates metabolism
Calcium Phosphorus Iron Iodine Zinc Fluoride H2O. Dehydration. Demineralization |
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Metabolic rate-rate of heat liberation during the chemical reactions?
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Direct calorimetry:direct measurement of body heat liberation in a given time in calorimeter (performed only for research purposes)
Indirect calorimetry: rate calculated from the rate of oxygen utilization by using energy equivalent. Respiratory coefficient: ratio of exhaled CO2 volume to oxygen uptake. For glucose and other carbs it is equal 1,for lipids 0.7 for protein 0.8 |
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Energy output?
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Basal metabolic rate
Digesting, absorbing food processing rate Body temperature maintaining rate Physical activity rate |
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Rubner’s law:
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the metabolic rate of birds and mammals that maintain a relatively constant body temperature should ultimately be proportional to their surface area: if to calculate intensity of basal metabolic rate per 1kg body weight of different mammals or people with different body mass and height the coefficient will be different, but per 1m² of body surface it is do not differ significantly:
Human: 64.3 kg body weight – 32.1kcal/kg-1042/1m². Mouse:0.018 kg – 654 kcal/kg –1188/m² Dog: 15.2kg –51.5kcal/kg – 1039/m² |
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Metabolic rate changes are affected by:
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Age
Gender Hormonal disturbances Physical activity Intellectual activity Malnutrition |
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Body temperature. Regulation?
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Isothermia – constant body temperature independently from changes in surroundings. (birds, mammals)
Is controlled by balancing heat production and heat loss Average normal body temperature is 98-98.6F or 36.6-36.9C. Fluctuate during activity and rest phases. New born have imperfect ability to maintain body temperature |
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Chemical thermoregulation :heat production in biochemical reaction?
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Decrease in optimum surrounding temperature increase in thermo production and metabolic rate in
Muscles(site of the most intensive thermoregulation) Liver Kidney |
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Physical thermoregulation: intensity of heat conduction?
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Comfort zone of surrounding is 68-70F
Hyperthermia (more then 37C) -Heat radiation and convection in increase surroundings temperature -Vasodilatation,sweating and evaporation(75% of heat loss)(humidity, wind in surrounding) Hypothermia (less then 35C) Vasoconstriction Piloerection Shivering Pose Clothing |
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Regulation of body temperature:
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Hypothalamus (preoptic area) controls body temperature;cold sensitive and heat sensitive neurons; posterior hypothalamus combine signals from preoptic area and elsewhere in body to control body temperature
Autonomic nervous system: Cholinergic: sweating Sympathetic: uncouple oxidative phosphorylation Acclimatization (animal’s thyroid gland increase in cold environment) Fever (pyrogens) Heatstroke: dizziness, abdominal distress,, loss of consciousness Frostbite Artificial hypothermia (during heart surgery |
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Hyperammonemias is?
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Caused by inborn errors ureagenesis organic acidemias, liver immaturity and liver failure
Neonatal ammonemias are characterized by vomiting, lethargy, lack of appetite, seizures and coma |